CLINICAL STUDIES Clinical features and predictors of outcome in acute hepatitis A and hepatitis E virus hepatitis on cirrhosis Yellapu Radha Krishna, Vivek Anand Saraswat, Khaunish Das, Goel Himanshu, Surender Kumar Yachha, Rakesh Aggarwal and Gour Choudhuri Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India Keywords Ascites – acute-on-chronic liver failure – hepatic encephalopathy Correspondence Y. Radha Krishna, Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, India Tel: 197 0488 3149 Fax: 197 (0)40 2784 0980 e-mail: radhayellapu@yahoo.co.in Received 24 February 2008 Accepted 26 August 2008 DOI:10.1111/j.1478-3231.2008.01887.x Abstract Background and Objectives: Acute hepatitis A and E are recognized triggers of hepatic decompensation in patients with cirrhosis, particularly from the Indian subcontinent. However, the resulting acute-on-chronic liver failure (ACLF) has not been well characterized and no large studies are available. Our study aimed to evaluate the clinical profile and predictors of 3-month mortality in patients with this distinctive form of liver failure. Methods: ACLF was diagnosed in patients with acute hepatitis A or E [abrupt rise in serum bilirubin and/or alanine aminotransferase with positive immunoglobulin M anti-hepatitis A virus (HAV)/anti-hepatitis E virus (HEV)] presenting with clinical evidence of liver failure (significant ascites and/or hepatic encephalopathy) and clinical, biochemical, endoscopic (oesophageal varices at least grade II in size), ultrasonographical (presence of nodular irregular liver with porto- systemic collaterals) or histological evidence of cirrhosis. Clinical and laboratory profile were evaluated, predictors of 3-month mortality were determined using univariate and multivariate logistic regression and a prognostic model was constructed. Receiver- operating curves were plotted to measure performance of the present prognostic model, model for end-stage liver disease (MELD) score and Child–Turcotte–Pugh (CTP) score. Results: ACLF occurred in 121 (3.75%) of 3220 patients (mean age 36.3  18.0 years; M:F 85:36) with liver cirrhosis admitted from January 2000 to June 2006. It was due to HEV in 80 (61.1%), HAV in 33 (27.2%) and both in 8 (6.1%). The underlying liver cirrhosis was due to HBV (37), alcohol (17), Wilson’s disease (8), HCV (5), autoimmune (6), Budd-Chiari syndrome (2), haemochromatosis (2) and was cryptogenic in the rest (42). Common presentations were jaundice (100%), ascites (78%) and hepatic encephalopathy (55%). Mean (SD) CTP score was 11.4  1.6 and mean MELD score was 28.6  9.06. Three-month mortality was 54 (44.6%). Complica- tions seen were sepsis in 42 (31.8%), renal failure in 45 (34%), spontaneous bacterial peritonitis in 27 (20.5%), UGI bleeding in 15(11%) and hyponatraemia in 50 (41.3%). On univariate analysis, ascites, hepatic encephalopathy, renal failure, GI bleeding, total bilirubin, hyponatraemia and coagulopathy were significant predictors of mortality. Multivariate analysis revealed grades 3 and 4 HE [odds ratio (OR 32.1)], hyponatrae- mia (OR 9.2) and renal failure (OR 16.8) as significant predictors of 3-month mortality and a prognostic model using these predictors was constructed. Areas under the curve for the present predicted prognostic model, MELD, and CTP were 0.952, 0.941 and 0.636 respectively. Conclusions: ACLF due to hepatitis A or E super infection results in significant short-term mortality. The predictors of ominous outcome include grades 3 and 4 encephalopathy, hyponatraemia and renal failure. Present prognostic model and MELD scoring system were better predictors of 3-month outcome than CTP score in these patients. Early recognition of those with dismal prognosis may permit timely use of liver replacement/supportive therapies. Acute on chronic liver failure (ACLF) is a decompensation of chronic liver disease (CLD) with ascites, encephalopathy or coagulopathy. Acute insults in a patient with CLD may be caused by sepsis, gastrointestinal (GI) bleeding, hepatotoxic drugs, hepatic and portal vein thrombosis, spontaneous bacter- ial peritonitis, hepatocellular carcinoma or super infection with acute viral hepatitis A–E (1). A precise definition of this clinical condition is lacking in the scientific literature. ACLF is defined by Jalan as an ‘acute deterioration in liver function over a period of 2–4 weeks leading to severe worsening of clinical status with a high SOFA/APACHE II score with jaundice and either hepatic encephalopathy or renal failure’ (2). Characteristic complications of ACLF are renal dysfunction and multiorgan failure (3). Therapeutic measures aim at the stabilization of the liver function until regeneration of the liver has been achieved or a suitable organ for liver transplantation is available (4). Extracorporeal liver-assist devices have been at- tempted as a bridge to liver transplant (5–8). Liver transplant has changed the gloomy outlook of the disease and post-transplant Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation Liver International (2009) 392 c  2009 The Authors. Journal compilation c  2009 Blackwell Publishing Ltd Liver International ISSN 1478-3223